Current Insights on Neoplasms and Adequate Dental Care for Patients with Oral Cancer / Actualización sobre Neoplasmas y su Correcta Atención Odontológica en Pacientes con Cancer Oral

The present study aimed to review the literature on the main complications of antineoplastic therapies and the degree of knowledge of dental surgeons about these complications. A bibliographic search was conducted in the main health databases PUBMED (www.pubmed.gov) and Scholar Google (www.scholar.google.com.br), in which studies published from 1987 to 2023 were collected. Laboratory studies, case reports, systematic and literature reviews, which were developed in living individuals, about the main neoplastic genes and their relationship with the cells of individuals affected by neoplasms in the head and neck region, and studies on the care with this group of patients, were included. Therefore, articles that did not deal with neoplasm and the main complications of antineoplastic therapies were excluded. Neoplasm is a clonal disorder, caused by mutations, resulting from changes in the genetic structure of cells. Each healthy cell has instructions on how to grow and divi de. In the presence of any error in these instructions (mutation), it can result in a diseased cell that, when proliferating, may cause a tumor. Countless knowledge has been accumulated over the years on the main characteristics of neoplasms, whether they are cancer cell biology, carcinogenesis mechanism, neoplasms of the maxillofacial system and sequels of antineoplastic treatments. In this context, methods have been developed that offer a better quality of life for patients diagnosed with this pathology, as well as preventive vaccine models that may, in the not too distant future, contribute to this goal to be successfully achieved.

El presente estudio tuvo como objetivo revisar la literatura sobre las principales complicaciones de las terapias antineoplásicas y el grado de conocimiento de los odontólogos sobre este abordaje. Se realizó una búsqueda bibliográfica en las principales bases de datos de salud PUBMED (www.pubmed.gov) y Scholar Google (www.scholar.google.com.br), en la que se recopilaron estudios publicados entre 1987 y 2023. Fueron incluidos estudios de laboratorio, relatos de casos, revisiones de la literatura y revisiones sistemáticas, desarrolladas en individuos vivos, que incluyeran los principales genes neoplásicos y su relación con las células de individuos afectados por neoplasias en la cabeza y el cuello. También, se tuvieron en cuenta estudios relacionados con la atención a este grupo de pacientes. La neoplasia es un trastorno clonal, causado por mutaciones, como resultado de cambios en la estructura genética de las células. Cada célula sana tiene instrucciones sobre cómo crecer y dividirse. En presencia de cualquier error en estas instrucciones (mutación), puede provocar una célula alterada que, al proliferar, puede causar un tumor. Se han acumulado innumerables conocimientos a lo largo de los años sobre las principales características de las neoplasias, ya sea sobre biología de células cancerosas, el mecanismo de la carcinogénesis, la neoplasias del sistema maxilofacial y las diferentes secuelas de tratamientos antineoplásicos. En este contexto, se han desarrollado métodos que ofrecen una mejor calidad de vida para los pacientes diagnosticados con esta patología, así como modelos de vacunas preventivas que, en un futuro no muy lejano, pueden contribuir a alcanzar este objetivo con éxito.

Stoichioproteomics study of differentially expressed proteins and pathways in head and neck cancer / Estudo estequioproteômico de proteínas e vias expressas diferencialmente no câncer de cabeça e pescoço

Abstract Hypoxia is a prominent feature of head and neck cancer. However, the oxygen element characteristics of proteins and how they adapt to hypoxia microenvironments of head and neck cancer are still unknown. Human genome sequences and proteins expressed data of head and neck cancer were retrieved from pathology atlas of Human Protein Atlas project. Then compared the oxygen and carbon element contents between proteomes of head and neck cancer and normal oral mucosa-squamous epithelial cells, genome locations, pathways, and functional dissection associated with head and neck cancer were also studied. A total of 902 differentially expressed proteins were observed where the average oxygen content is higher than that of the lowly expressed proteins in head and neck cancer proteins. Further, the average oxygen content of the up regulated proteins was 2.54% higher than other. None of their coding genes were distributed on the Y chromosome. The up regulated proteins were enriched in endocytosis, apoptosis and regulation of actin cytoskeleton. The increased oxygen contents of the highly expressed and the up regulated proteins might be caused by frequent activity of cytoskeleton and adapted to the rapid growth and fast division of the head and neck cancer cells. The oxygen usage bias and key proteins may help us to understand the mechanisms behind head and neck cancer in targeted therapy, which lays a foundation for the application of stoichioproteomics in targeted therapy and provides promise for potential treatments for head and neck cancer.

Resumo A hipóxia é uma característica proeminente do câncer de cabeça e pescoço. No entanto, as características do elemento oxigênio das proteínas e como elas se adaptam aos microambientes de hipóxia do câncer de cabeça e pescoço ainda são desconhecidas. Sequências do genoma humano e dados expressos de proteínas de câncer de cabeça e pescoço foram recuperados do atlas de patologia do projeto Human Protein Atlas. Em seguida, comparou o conteúdo do elemento de oxigênio e carbono entre proteomas de câncer de cabeça e pescoço, e células epiteliais escamosas da mucosa oral normal, localizações do genoma, vias e dissecção funcional associada ao câncer de cabeça e pescoço também foram estudadas. Um total de 902 proteínas expressas diferencialmente foi observado onde o conteúdo médio de oxigênio é maior do que as proteínas expressas de forma humilde em proteínas de câncer de cabeça e pescoço. Além disso, o conteúdo médio de oxigênio das proteínas reguladas positivamente foi 2,54% maior do que das outras. Nenhum de seus genes codificadores foi distribuído no cromossomo Y. As proteínas reguladas positivamente foram enriquecidas em endocitose, apoptose e regulação do citoesqueleto de actina. O conteúdo aumentado de oxigênio das proteínas altamente expressas e reguladas pode ser causado pela atividade frequente do citoesqueleto e adaptado ao rápido crescimento e divisão das células cancerosas de cabeça e pescoço. O viés do uso de oxigênio e as proteínas-chave podem nos ajudar a entender os mecanismos por trás do câncer de cabeça e pescoço na terapia direcionada, o que estabelece uma base para a aplicação da estequioproteômica na terapia direcionada e oferece uma promessa para potenciais tratamentos para o câncer de cabeça e pescoço.

Biological function and clinical significance of long non-coding RNA LINC00342 in head and neck squamous carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the relationship between the long-non-coding RNA LINC00342 expression and the clinicopathological parameters of head and neck squamous cell carcinoma (HNSCC) and the biological function of LINC00342 in HNSCC cells. Methods: The expression level of LINC00342 in the HNSCC was analyzed using transcriptome sequencing data from TCGA (The Cancer Genome Atlas) database, and the expressions of LINC00342 in laryngeal squamous cell carcinoma tissues (LSCC) of 27 patients in the First Hospital of Shanxi Medical University were detected by transcriptome sequencing. The expression levels of LINC00342 in human embryonic lung diploid cells 2BS, HNSCC cell lines FD-LSC-1, CAL-27 and Detroit562 were determined by real-time quantitative polymerase chain reaction (qPCR). RNAi (RNA interference) was used for LINC00342 knockdown in HNSCC cell lines, and the changes of malignant phenotype in the tumor cells after LINC00342 knockdown were examined by cell counting kit-8 (CCK-8), colony formation, flow cytometry, transwell invasion and migration assays. Bioinformatics analysis was performed to construct a LINC00342-centered competing endogenous RNA (ceRNA) regulatory network, and GO (Gene Ontology) enrichment analysis was performed. Statistical analysis and graphing were performed using SPSS 25.0 software and GraphPad Prism 6 software. Results: Mean LINC00342 levels in HNSCC tissues and TCGA database were higher than that in normal control tissues, but with no significantly statistical difference (P=0.522). LINC00342 expression levels were positively correlated with cervical lymph node metastasis and pathological grade in patients with HNSCC, with higher expression in male patients than in female patients (P<0.05). Transcriptome sequencing analysis showed that mean expression level of LINC00342 in LSCC tissues of 27 patients was significantly higher than that in the paired adjacent normal mucosa tissues (t=1.56, P=0.036). LINC00342 expression was significantly upregulated in HNSCC cell lines FD-LSC-1, CAL-27 and Detroit562 (t-values of -12.17, -23.26 and -388.57, respectively; all P<0.001). Knockdown of LINC00342 by transfecting si-LINC00342-1 and si-LINC00342-2 inhibited HNSCC cell proliferation (t-values of 8.95 and 4.84, 2.70 and 5.55, 2.02 and 3.70, respectively), colony formation (t-values of 6.66 and 6.17, 7.38 and 11.65, 4.90 and 5.79, respectively), migration (t-values of 8.21 and 7.19, 5.76 and 6.46, 6.28 and 9.92, respectively) and invasion abilities (t-values of 9.29 and 10.25, 11.30 and 11.36, 8.02 and 8.66, respectively), but promoting apoptosis in cell lines FD-LSC-1 and CAL-27 (t-values of -2.21 and -5.83, -3.05 and -5.25 respectively) (all P-values<0.05). The LINC00342-centered ceRNA network consists of 10 downregulated microRNA and 647 upregulated mRNA nodes. GO analysis results indicated that LINC00342-regulated mRNAs were enriched in 22 biological processes, 32 molecular functions, and 12 cellular components. Conclusion: High level of LINC00342 is associated with the malignant progression of HNSCC. LINC00342 promotes the proliferation, migration, invasion, and antagonizes apoptosis of HNSCC cells, which serves as a potential molecular marker in HNSCC.

Stoichioproteomics study of differentially expressed proteins and pathways in head and neck cancer / Estudo estequioproteômico de proteínas e vias expressas diferencialmente no câncer de cabeça e pescoço

Hypoxia is a prominent feature of head and neck cancer. However, the oxygen element characteristics of proteins and how they adapt to hypoxia microenvironments of head and neck cancer are still unknown. Human genome sequences and proteins expressed data of head and neck cancer were retrieved from pathology atlas of Human Protein Atlas project. Then compared the oxygen and carbon element contents between proteomes of head and neck cancer and normal oral mucosa-squamous epithelial cells, genome locations, pathways, and functional dissection associated with head and neck cancer were also studied. A total of 902 differentially expressed proteins were observed where the average oxygen content is higher than that of the lowly expressed proteins in head and neck cancer proteins. Further, the average oxygen content of the up regulated proteins was 2.54% higher than other. None of their coding genes were distributed on the Y chromosome. The up regulated proteins were enriched in endocytosis, apoptosis and regulation of actin cytoskeleton. The increased oxygen contents of the highly expressed and the up regulated proteins might be caused by frequent activity of cytoskeleton and adapted to the rapid growth and fast division of the head and neck cancer cells. The oxygen usage bias and key proteins may help us to understand the mechanisms behind head and neck cancer in targeted therapy, which lays a foundation for the application of stoichioproteomics in targeted therapy and provides promise for potential treatments for head and neck cancer.

A hipóxia é uma característica proeminente do câncer de cabeça e pescoço. No entanto, as características do elemento oxigênio das proteínas e como elas se adaptam aos microambientes de hipóxia do câncer de cabeça e pescoço ainda são desconhecidas. Sequências do genoma humano e dados expressos de proteínas de câncer de cabeça e pescoço foram recuperados do atlas de patologia do projeto Human Protein Atlas. Em seguida, comparou o conteúdo do elemento de oxigênio e carbono entre proteomas de câncer de cabeça e pescoço, e células epiteliais escamosas da mucosa oral normal, localizações do genoma, vias e dissecção funcional associada ao câncer de cabeça e pescoço também foram estudadas. Um total de 902 proteínas expressas diferencialmente foi observado onde o conteúdo médio de oxigênio é maior do que as proteínas expressas de forma humilde em proteínas de câncer de cabeça e pescoço. Além disso, o conteúdo médio de oxigênio das proteínas reguladas positivamente foi 2,54% maior do que das outras. Nenhum de seus genes codificadores foi distribuído no cromossomo Y. As proteínas reguladas positivamente foram enriquecidas em endocitose, apoptose e regulação do citoesqueleto de actina. O conteúdo aumentado de oxigênio das proteínas altamente expressas e reguladas pode ser causado pela atividade frequente do citoesqueleto e adaptado ao rápido crescimento e divisão das células cancerosas de cabeça e pescoço. O viés do uso de oxigênio e as proteínas-chave podem nos ajudar a entender os mecanismos por trás do câncer de cabeça e pescoço na terapia direcionada, o que estabelece uma base para a aplicação da estequioproteômica na terapia direcionada e oferece uma promessa para potenciais tratamentos para o câncer de cabeça e pescoço.

OShnscc: a novel user-friendly online survival analysis tool for head and neck squamous cell carcinoma based on RNA expression profiles and long-term survival information / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Head and neck squamous cell carcinoma (HNSCC), as the most common type (>90%) of head and neck cancer, includes various epithelial malignancies that arise in the nasal cavity, oral cavity, pharynx, and larynx. In 2020, approximately 878 ‍ 000 new cases and 444 000 deaths linked to HNSCC occurred worldwide (Sung et al., 2021). Due to the associated frequent recurrence and metastasis, HNSCC patients have poor prognosis with a five-year survival rate of 40%-50% (Jou and Hess, 2017). Therefore, novel prognostic biomarkers need to be developed to identify high-risk HNSCC patients and improve their disease outcomes.

FAM64A promotes HNSCC tumorigenesis by mediating transcriptional autoregulation of FOXM1 / 国际口腔科学杂志·英文版

Head and neck squamous cell carcinoma (HNSCC) still lacks effective targeted treatment. Therefore, exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC. Here, we reported that the expression levels of family with sequence similarity 64, member A (FAM64A) were significantly higher in HNSCC tissues and cell lines. In addition, FAM64A overexpression was found to be strongly associated with an unfavorable prognosis of HNSCC. Both in vitro and in vivo evidence showed that FAM64A depletion suppressed the malignant activities of HNSCC cells, and vice versa. Moreover, we found that the FAM64A level was progressively increased from normal to dysplastic to cancerous tissues in a carcinogenic 4-nitroquinoline-1-oxide mouse model. Mechanistically, a physical interaction was found between FAM64A and forkhead box protein M1 (FOXM1) in HNSCC cells. FAM64A promoted HNSCC tumorigenesis not only by enhancing the transcriptional activity of FOXM1, but also, more importantly, by modulating FOXM1 expression via the autoregulation loop. Furthermore, a positive correlation between FAM64A and FOXM1 was found in multiple independent cohorts. Taken together, our findings reveal a previously unknown mechanism behind the activation of FOXM1 in HNSCC, and FAM64A might be a promising molecular therapeutic target for treating HNSCC.

Identification and clinical validation of gene signatures with grade and survival in head and neck carcinomas

This study aimed to explore gene expression profiles that drive malignancy from low- to high-grade head and neck carcinomas (HNC), as well as to analyze their correlations with survival. Gene expressions and clinical data of HNC were downloaded from the Gene Expression Omnibus (GEO) repository. The significantly differential genes (SDGs) between low- and high-grade HNC were screened. Cox regressions were performed to identify prognostic SDGs of progression-free survival (PFS) and disease-specific survival (DSS). The genes were experimentally validated by RT-PCR in clinical tissue specimens. Thirty-five SDGs were identified in 47 low-grade and 30 high-grade HNC samples. Cox regression analyses showed that CXCL14, SLC44A1, and UBD were significantly associated with DSS, and PPP2R2C and SLC44A1 were associated with PFS. Patients were grouped into high-risk or low-risk groups for prognosis based on gene signatures. High-risk patients had significantly shorter DSS and PFS than low-risk patients (P=0.033 and P=0.010, respectively). Multivariate Cox regression showed HPV (P=0.033), lymph node status (P=0.032), and residual status (P<0.044) were independent risk factors for PFS. ROC curves showed the risk score had better efficacy to predict survival both for DSS and PFS (AUC=0.858 and AUC=0.901, respectively). The results showed CXCL14 and SLC44A1 were significantly overexpressed in the low-grade HNC tissues and the UBD were overexpressed in the high-grade HNC tissues. Our results suggested that SDGs had different expression profiles between the low-grade and high-grade HNC, and these genes may serve as prognostic biomarkers to predict survival.

Low p27kip1 expression in head and neck squamous cell carcinoma: association with risk factors and adverse outcomes

Background: Squamous cell carcinoma (SCC) of head and neck is highly prevalent in South-asian countries, owing to high consumption of areca nut/gutka and chewing tobacco. p27kip1 is a tumor suppressor gene, thought to be downregulated in oral squamous cell carcinoma. Therefore, in the present study we used immunohistochemical analysis to investigate an association between low p27kip1 expression in SCC of the head and neck and adverse outcomes/risk factors. Methods: Total 105 cases of SCC of head and neck excision specimens were selected from records of pathology department archives that underwent surgeries at Liaquat National hospital, Karachi from January 2008 till December 2013. Clinical and pathologic characteristics of patients were evaluated and p27kip1 immunohistochemistry was applied on tumor blocks. Results: In our study, low expression of p27kip1 in SCC of head and neck was seen in 39(37.1%) cases while 66(62. 9%) of the cases showed high expression for p27kip1. Significant association of p27kip1 expression with pan/gutka usage (p = 0.004), and recurrence (p = 0.001) was noted; however, no significant association of p27kip1 expression with other clinicopathologic features was seen. Multivariate binary logistic regression showed cases with history of pan/gutka usage were more likely to show low p27kip1 expression. Similarly, we also found that recurrence was more likely to develop in patients with low expression of p27kip1 in comparison to cases showing high p27kip1 expression. Conclusion: Loss of p27kip1 expression is a significant event involved in the pathogenesis of SCC head and neck especially that of oral cavity. Significant association of gutka/areca nut with low p27kip1 expression in our study suggests that loss p27kip1 expression is a major event involved in areca nut induced SCC of head and neck in this part of the world; however, more large scale molecular based studies are required to validate this observation. Moreover, significant association of low p27kip1 expression with tumor recurrence suggests its importance as a prognostic biomarker in SCC of head and neck (AU)

Low expression of MSH2 DNA repair protein is associated with poor prognosis in head and neck squamous cell carcinoma

OBJECTIVE: This study aimed to investigate the expression of the MSH2 DNA repair protein in head and neck squamous cell carcinoma (HNSCC) in order to analyze its association with clinicopathologic factors and overall survival of patients. MATERIAL AND METHODS: Clinical data and primary lesions of HNSSC were collected from 55 patients who underwent surgical resection with postoperative radiotherapy in Montes Claros, state of Minas Gerais, Brazil, between 2000 and 2008. Immunohistochemical reactions were performed to analyze MSH2 protein expression. RESULTS: Bivariate analysis showed no significant correlation or association between MSH2 expression and clinicopathologic parameters by Mann-Whitney and Kruskal-Wallis tests. Patients with locoregional metastatic disease (OR=4.949, p<0.001) and lower MSH2 immunohistochemical expressions (OR=2.943, p=0.032) presented poorer survival for HNSCC by Cox regression models. CONCLUSIONS: Our data demonstrated that lower MSH2 expression might contribute to a higher clinic aggressiveness of HNSCC by promoting an unfavorable outcome. .

An overview of gene therapy in head and neck cancer.

Gene therapy is a new treatment modality in which new gene is introduced or existing gene is manipulated to cause cancer cell death or slow the growth of the tumor. In this review, we have discussed the different treatment approaches for cancer gene therapy; gene addition therapy, immunotherapy, gene therapy using oncolytic viruses, antisense ribonucleic acid (RNA) and RNA interference‑based gene therapy. Clinical trials to date in head and neck cancer have shown evidence of gene transduction and expression, mediation of apoptosis and clinical response including pathological complete responses. The objective of this article is to provide an overview of the current available gene therapies for head and neck cancer.

MicroRNAs em pacientes com história familiar de carcinoma epidermóide de cabeça e pescoço / MicroRNAs profile in patients with family history of head and neck cancer

Apesar da maioria dos casos de câncer de cabeça e pescoço ocorrer de maneira esporádica e geralmente estar relacionada à exposição crônica a álcool e tabaco, a história familiar e a suscetibilidade têm merecido especial interesse nas últimas duas décadas. O objetivo do presente estudo foi caracterizar o perfil clínico e epidemiológico de pacientes portadores de câncer de cabeça e pescoço e história familiar de câncer, avaliar o perfil de expressão dos miRNAs em amostras de sangue periférico de pacientes com carcinoma epidermóide de cabeça e pescoço (CECP) e história familial de câncer com seus respectivos parentes e checar, a partir da utilização de bancos de dados de miRNAs, os principais genes regulados e suas eventuais relações com neoplasias. Foram selecionados 74 casos usando o banco de dados do Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital A.C. Camargo, São Paulo no período de 2003 a 2011. Os critérios utilizados para caracterizar os casos familiais de CECP foram: 1) dois ou mais parentes de primeiro grau acometidos por CECP ou tumores relacionados; 2) Idade de aparecimento do CECP inferior a 45 anos em pelo menos um dos membros da família; 3) Aparecimento do CECP em qualquer idade em casos com ausência de exposição prévia ao tabaco e álcool ou qualquer outro fator etiológico conhecido. Os tumores considerados como relacionados ao CECP foram aqueles associados com o consumo de tabaco (pulmão, esôfago, estômago, pâncreas, fígado, rim, bexiga, útero e medula óssea) ou outros tumores epiteliais como carcinoma colorretal, mama e melanoma. Foram coletadas amostras de sangue periférico dos probandos e, quando possível, de um de seus parentes acometidos por câncer e realizada a análise de expressão de miRNAs por RT-qPCR. O sítio de tumor mais comum nos probandos foi cavidade oral (42%) seguido de laringe (31.5%)...

Although most cases of head and neck cancer (HNSCC) occur sporadically and generally are related to chronic exposure of alcohol and tobacco, family history and genetic susceptibility have earned special interest in the last two decades.The aims of this study were to characterize the clinical and epidemiological profile of patients with head and neck cancer and family history of cancer, evaluate the expression profile of miRNAs in peripheral blood samples from patients with HNSCC and familial history of cancer with their relatives and check, by using miRNAs databases, the main regulated genes and their possible relationship to cancer. A total of 74 cases were selected through pre-existing databases of the Department of Head and Neck Surgery and Otorhinolaryngology, AC Camargo Hospital, Sao Paulo from 2003 to 2011. The criteria used to characterize the familial cases of HNSCC were: 1) two or more first degree relatives affected by HNSCC or related tumors, 2) Age of onset of HNSCC less than 45 years in at least one of the family members, 3) Appearance of HNSCC at any age if no prior exposure to tobacco and alcohol or any other known etiologic factor. Tumors considered related HNSCC were those related to tobacco consumption (lung, esophagus, stomach, pancreas, liver, kidney, bladder, uterus and bone marrow) or other epithelial tumors such as colorectal carcinoma, breast and melanoma. Then, peripheral blood samples of these patients were collected and, when possible, of one of them relatives affected by cancer. Subsequently, the evaluation of miRNAs expression was did by RT-qPCR. The most common tumor sites of probands were oral cavity, with 31 cases (42%), followed by the larynx, 24 cases (31.5%). Among the 74 families, the number of affected relatives was 171, with 121 of first-degree and 50 of second and third degree. In this group there were 19 different tumor sites and the most common were: head and neck (18.6%), breast (16%), colon (13%), stomach (11%)...

Polimorfismos do gene da interleucina-13 nas posições -1055 C/T e +2044 G/A em pacientes com carcinoma espinocelular de cabeça e pescoço / Interleukin-13 gene polymorphisms at -1055 C/T and +2044 G/A positions in patients with squamous cell carcinoma of head and neck

O carcinoma espinocelular (CEC) é a neoplasia mais comum do trato aerodigestivo superior. A interleucina-13 (IL-13) é uma citocina imunorreguladora com polimorfismos relatados para seu gene associados com a mesma doença, especialmente asma e alergia. O presente estudo investigou se os polimorfismos do gene da IL-13 (posições 1055C/T no gene promotor da 1L-13 e +2044G/T exon 4) podem distinguir os pacientes com CEC de cabeça e pescoço de controles saudáveis. MÉTODO: O estudo analisou pacientes com CEC de cabeça e pescoço (n = 137) pareados por idade e sexo com um grupo de controles saudáveis (n = 127). A genotipagem do polimorfismo do gene da IL-13 foi executada pelo método de polimorfismo no comprimento de fragmentos de restrição baseado em reação em cadeia da polimerase. RESULTADOS: Não foram identificadas diferenças estatisticamente significativas nas frequências dos genótipos e alelos entre pacientes e controles em ambas as posições (p = 0,16). Além disso, não foi observada associação entre os genótipos investigados e outros fatores prognósticos, como idade, sexo, localização do tumor primário, tamanho do tumor e tabagismo. CONCLUSÃO: O presente estudo sugere que não há associação entre os polimorfismos do gene da IL-13 (nas posições -1055C/T e +2044GI A) e suscetibilidade dos pacientes a CEC de cabeça e pescoço.

Squamous cell carcinoma (SCC) is the most common malignancy that involves the upper aerodigestive tract. Interleukin-13 (IL-13) is an immunoregulatory cytokine that has been reported to have some polymorphisms in it gene associated with same disease especially asthma and allergy. The present study aimed to investigate whether the polymorphisms of IL-13 gene (at positions of 1055C/T in the promoter of1L-13 gene and +2044G/T exon-4) differ in patients with head and neck SCC from healthy controls. METHODS: This study was investigated in patient with head and neck SCC (n = 137) and age- and sex-matched healthy controls (n = 127). Genotyping of IL-13 gene polymorphism was performed using polymerase chain reaction-based restriction fragment length polymorphism method. RESULTS: No statistically significant differences were found in the frequencies of genotypes and alleles between patients and control group at both sites (p = 0.16). In addition, no association was observed between investigated genotypes and other potential prognostic factors such as age, sex, primary tumor site, tumor size and smoking. CONCLUSION: This study suggests that there is no association between IL-13 gene polymorphisms (at position -1055C/T and +2044GI A) and susceptibility of the patients to SCC of head and neck.

Prevalência de lesões cutâneas actínicas em pacientes com carcinoma basocelular do segmento cefálico: um estudo caso-controle / Prevalence of actinic skin lesions in patients with basal cell carcinoma of the head: a case-control study

OBJETIVO: Avaliar a prevalência de lesões cutâneas actínicas em portadores de carcinoma basocelular do segmento cefálico. MÉTODOS: Foi conduzido estudo tipo caso-controle. Os casos, constituídos por pacientes com carcinoma basocelular sólido, primário, menor que dois centímetros, no segmento cefálico; e controles, por pacientes com outras dermatoses. Foram analisadas variáveis constitucionais, comportamentais e lesões actínicas. RESULTADOS: Avaliaram-se 120 casos e 360 controles. Mílio facial (OR = 2,3), leucodermia puntacta de membros superiores (OR = 2,9) e cutis romboidalis nuchae (OR = 1,8) associaram-se à neoplasia independentemente das demais variáveis, sugerindo um fenótipo de risco. Houve ainda associação com fenótipos claros, genética familiar e exposição solar cumulativa. Queimadura solar, tabagismo e alcoolismo não foram identificados como fatores de risco. O uso de fotoprotetores não evidenciou proteção; porém, o grupo controle era composto por pacientes dermatológicos, aos quais são indicados fotoprotetores regularmente. CONCLUSÃO: Lesões actínicas foram mais prevalentes em portadores de carcinoma basocelular sólido do segmento cefálico que em controles, especialmente mílio, cutis romboidalis nuchae e leucodermia puntacta, independentemente dos demais fatores de risco conhecidos.

OBJECTIVE: To evaluate the prevalence of actinic skin lesions in patients with basal cell carcinoma of the head. METHODS: A case-control study was carried out. Cases were patients with primary, solid basal cell carcinoma of the head, less than two centimeters in diameter; and as controls, patients with other dermatoses. Constitutional and behavioral variables were analyzed, as well as actinic lesions. RESULTS: One hundred twenty cases and 360 controls were evaluated. Facial milia (OR = 2.3), leukoderma punctata of the upper limbs (OR = 2.9), and cutis rhomboidalis nuchae (OR = 1.8) were associated with neoplasms regardless of other variables, suggesting a risk phenotype. There was also association with light hair and eye color phenotypes, family genetics, and cumulative sun exposure. Sunburn, smoking, and alcoholism were not identified as risk factors. The use of sunscreens showed no evidence of protection; however, the control group consisted of dermatology patients who are often prescribed sunscreens. CONCLUSION: Actinic lesions were more prevalent in patients with solid basal cell carcinoma of the head than in controls, especially milia, cutis rhomboidalis nuchae, and leukoderma punctata, regardless of other known risk factors.

Câncer de cabeça e pescoço: polimorfismos genéticos e metabolismo do folato / Head and neck cancer: genetic polymorphisms and folate metabolism

Evidências epidemiológicas sugerem que variantes genéticas que codificam enzimas envolvidas no metabolismo do folato podem modular o risco de câncer de cabeça e pescoço por alterar a metilação, síntese de DNA e estabilidade genômica. OBJETIVOS: Realizar uma revisão bibliográfica sobre polimorfismos genéticos envolvidos no metabolismo do folato e o risco de câncer de cabeça e pescoço. METODOLOGIA: Realizou-se uma busca eletrônica na base de dados Medline, selecionando estudos em câncer de cabeça do pescoço e polimorfismos envolvidos no metabolismo do folato. RESULTADOS: A associação do polimorfismo MTHFR C677T no risco dessa neoplasia foi avaliada em nove estudos e três deles mostraram associação com essa doença. Os polimorfismos MTR A2756G e MTRR A66G e RFC1 A80G também foram associados com aumento de risco para o câncer de cabeça e pescoço. O polimorfismo MTHFD1 G1958A não mostra associação com o risco dessa doença e os resultados da avaliação do polimorfismo MTHFR A1298C nesse tipo de neoplasia são contraditórios. Outros polimorfismos envolvidos no metabolismo do folato ainda não foram estudados nesse tipo de neoplasia. CONCLUSÃO: Concluímos que polimorfismos envolvidos no metabolismo do folato podem modular o risco desse tipo de tumor, no entanto, esses resultados precisam ser comprovados em diferentes populações.

Epidemiological evidence suggests that genetic variants encoding enzymes involved in folate metabolism may modulate HNSCC risk by altering DNA methylation synthesis and genomic estability. AIM: A review of the literature on genetic polymorphisms involved in folate metabolism and risk of head and neck cancer was carried out. METHODOLOGY: An electronic search was made on the Medline database to select papers on head and neck cancer and polymorphisms involved in folate metabolism. RESULTS: The association between MTHFR C677T polymorphism and the risk of this tumor type was evaluated in nine studies; there was an association with this disease in three papers. The MTR A2756G and MTRR A66G and RFC1 A80G polymorphisms were also associated with increased risk for HNSCC. MTHFD1 G1958A polymorphism was not associated with increased risk of this disease; the evaluation results of the MTHFR A1298C polymorphism in this neoplasm were contradictory. Other polymorphisms involved in folate metabolism were not studied for this neoplasm. CONCLUSION: We conclude that polymorphisms involved in folate metabolism may modulate the risk of head and neck cancer, however, these results need to be demonstrated in different populations.

Loss of Y-chromosome does not correlate with age at onset of head and neck carcinoma: a case-control study

Loss of Y-chromosome has been correlated with older age in males. Furthermore, current evidence indicates that Y-chromosome loss also occurs in several human tumors, including head and neck carcinomas. However, the association between Y nullisomy and the occurrence of neoplasias in elderly men has not been well established. In the present study, the association between Y-chromosome loss and head and neck carcinomas was evaluated by comparison to cells from peripheral blood lymphocytes and normal mucosa of cancer-free individuals matched for age using dual-color fluorescence in situ hybridization. Twenty-one patients ranging in age from 28 to 68 years were divided into five-year groups for comparison with 16 cancer-free individuals matched for age. The medical records of all patients were examined to obtain clinical and histopathological data. None of the patients had undergone radiotherapy or chemotherapy before surgery. In all groups, the frequency of Y-chromosome loss was higher among patients than among normal reference subjects (P < 0.0001) and was not age-dependent. These data suggest that Y-chromosome loss is a tumor-specific alteration not associated with advanced age in head and neck carcinomas.

Head and neck paragangliomas: clinical and molecular genetic classification

Head and neck paragangliomas are tumors arising from specialized neural crest cells. Prominent locations are the carotid body along with the vagal, jugular, and tympanic glomus. Head and neck paragangliomas are slowly growing tumors, with some carotid body tumors being reported to exist for many years as a painless lateral mass on the neck. Symptoms depend on the specific locations. In contrast to paraganglial tumors of the adrenals, abdomen and thorax, head and neck paragangliomas seldom release catecholamines and are hence rarely vasoactive. Petrous bone, jugular, and tympanic head and neck paragangliomas may cause hearing loss. The internationally accepted clinical classifications for carotid body tumors are based on the Shamblin Class I-III stages, which correspond to postoperative permanent side effects. For petrous-bone paragangliomas in the head and neck, the Fisch classification is used. Regarding the molecular genetics, head and neck paragangliomas have been associated with nine susceptibility genes: NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2 (SDH5), and TMEM127. Hereditary HNPs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations are not uncommon in such patients. Head and neck paragangliomas are rarely associated with mutations of VHL, RET, or NF1. The research on SDHA, SDHAF2 and TMEM127 is ongoing. Multiple head and neck paragangliomas are common in patients with SDHD mutations, while malignant head and neck paraganglioma is mostly seen in patients with SDHB mutations. The treatment of choice is surgical resection. Good postoperative results can be expected in carotid body tumors of Shamblin Class I and II, whereas operations on other carotid body tumors and other head and neck paragangliomas frequently result in deficits of the cranial nerves adjacent to the tumors. Slow growth and the tendency of hereditary head and neck paragangliomas to be multifocal may justify less aggressive treatment strategies.

Protective association exhibited by the single nucleotide polymorphism (SNP) rs1052133 in the gene human 8-oxoguanine DNA glycosylase (hOGG1) with the risk of squamous cell carcinomas of the head & neck (SCCHN) among north Indians.

Background & objectives: Imbalances in compactly regulated DNA repair pathways in the form of single nucleotide polymorphisms (SNPs) within vital DNA repair genes may result in insufficient DNA repair and increase in DNA breaks thus rendering the human system vulnerable to the debilitatory effects of grave diseases like cancers. The present study involves investigation of association of the non-synonymous SNP rs1052133 (C8069G/Ser326Cys) located in the exonic region of the gene human 8-oxoguanine DNA glycosylase (hOGG1) with the risk of squamous cell carcinomas of the head and neck (SCCHN). Methods: Case-control based genetic association study was performed among 575 (250 SCCHN cases and 325 normal healthy controls) sub-population cluster-matched (Indo-Europeans linguistic subgroup + Caucasoid morphological subtype) samples from the north Indian States of Uttar Pradesh and Uttarakhand using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing analysis. Results: Our results demonstrated statistically significant protective association for the heterozygous CG [Odds Ratio (OR) 0.6587, 95% Confidence Interval (CI) 0.4615 to 0.9402, P=0.0238], homozygous mutant GG (OR 0.2570, 95% CI 0.1070 to 0.6175, P=0.0013) and combined mutant CG + GG (OR 0.6057, 95% CI 0.4272 to 0.8586, P=0.0059) genotypes. Interpretation & conclusions: The results indicate that the polymorphism rs1052133 is strongly associated with SCCHN susceptibility and the mutant (G) allele might be a protective factor for SCCHN among north Indian subpopulations.

Association and treatment response to capecitabine-based chemoradiotherapy with CYP2C9 polymorphism in head and neck cancer.

Aims : The aim of the present study is to investigate the association of polymorphism in cytochrome P450 2C9 (CYP2C9) with head and neck squamous cell carcinoma (HNSCC) and response in patients receiving chemoradiotherapy. Materials and Methods : One hundred ten males suffering from locally advanced head and neck squamous cell carcinoma and an equal number of healthy controls were genotyped for CYP2C9*2 and CYP2C9*3, leading to poor metabolizers (PMs) by PCR-based RFLP. Each case was assessed thoroughly for treatment response following WHO criteria. Results : The frequency of heterozygous genotypes of both CYP2C9*2 (27.3%) and CYP2C9*3 (20.1%) were found to be significantly higher in the HNSCC cases as compared to the healthy controls. Tobacco intake in the form of chewing or smoking and alcohol intake resulted in several fold increase in the risk to HNSCC in the cases carrying variant genotypes of CYP2C9*2 or CYP2C9*3. Further, majority of the cases assessed for response (134) carrying variant alleles of both CYP2C9*2 (65.3%) or CYP2C9*3 (70.58%) were found to respond poorly to the radio-chemotherapy. Conclusions : The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome underlining the importance of pretherapeutic genotyping in determining the treatment schedule.